The overall goal of this project is to define the mechanisms whereby electrolyte and water are secreted by the eccrine sweat glands. Human or monkey eccrine sweat glands will be isolated, cannulated and stimulated in vitro and their secretory response to various pharmacological agents will be determined. Based on the dose response study, affinity constants for acetylcholine, methacholine, isoproterenol, phenylephrine, propranolol, phentolamine, and atropine will be determined in order to provide a measure of pharmacological responsiveness of the eccrine sweat glands. We have demonstrated over the past few years that the eccrine sweat glands are stimulated to secrete sweat by non-physiological agents such as prostaglandins and Ca ions-ionophore. Indirect evidence has also been accumulated that Ca ions influx into the cells, as stimulated by either acetylcholine or the Ca ions-ionophore A23187, initiates and maintains sweat secretion without altering the electrical resistance of the basal membrane. Strontium (Sr ions) can be substituted for Ca ions, but it seems to enter the cell via both an acetylcholine-mediated and a non-mediated route. Mn ions can partially substitute for Ca ions but all other divalent cations have failed to do so.